Somatic Cancer Driver Mutation Analysis in Endometriosis with Tumor-like Presentations: A Case Series Study

Background/Objectives: Endometriosis manifests as ectopic endometrial tissue outside the uterine cavity. This lesion can sometimes appear at unusual anatomical sites or within the intestinal tract, growing and mimicking cancer. Such tumor-like endometriosis lesions are relatively uncommon and biologically intriguing. Methods: This study is a retrospective case series of 14 patients presenting with tumor-like endometriosis at a single institution between 2007 and 2023. Laser capture microdissection was used to isolate epithelial cells from endometriotic glands in tissue sections from formalin-fixed, paraffin-embedded blocks, and the microdissected epithelium was analyzed for cancer driver mutations. Results: Unlike conventional endometriosis, these tumor-like lesions were generally sizable and clinically presented in the groin area, aortic wall, omentum, bowel wall, or lymph nodes, all of which raised suspicion for malignancy, despite 11 (78.6%) of the 14 cases having a history of or clinical signs of endometriosis. A total of 11 cancer-driver mutations were identified in 6 of the 14 patients, with four patients harboring multiple mutations. Recurrent mutations included KRAS-activating mutations in four cases and ARID1A-inactivating mutations in two cases. Additional mutations involved PIK3CA, CTNNB1, CHD4, MYD88, and STAG2. Conclusions: This study detected mutations in KRAS, ARID1A, PIK3CA, CTNNB1, and MYD88 in endometriotic lesions, consistent with previous literature, and identified newly reported mutations in CHD4 and STAG2. Not every tumor-like lesion harbored cancer driver mutations.